In vitro evaluation of an antibacterial microsphere platform integrating reactive oxygen species-mediated photodynamic therapy and sustained quercetin release for gram-positive bacterial regrowth suppression

초록

Photodynamic therapy (PDT) exhibits high antibacterial activity due to reactive oxygen species (ROS)-mediated killing; however, it suffers from oxygen dependence and post-treatment bacterial regrowth. Herein, we developed multifunctional and infection microenvironment (IME)-responsive antibacterial microsphere microfluidic emulsification technology with sequential surface functionalization to overcome these issues. The proposed technology included a quercetin-loaded poly(ethylene glycol)–poly(lactide-co-glycolide) core, polydomanine coating, in situ MnO2 formation, and chlorin e6 (Ce6) adsorption, yielding uniform multilayer particles with diameters of ∼130 μm. In a H2O2-rich and acidic IME, MnO2 rapidly degrades to generate O2 amplifying the Ce6-mediated 1O2 production under 670-nm irradiation for killing > 99% S. aureus and ∼80% E. coli bacterial species. The sustained quercetin release (∼8 μg/mL over 48 h) suppresses S. aureus regrowth (OD600 ∼0.15; 85% reduction vs. control) from residual populations (< 1% post-PDT) while showing limited efficacy and failing to prevent the regrowth of gram-negative E. coli . This dual-mechanism platform overcomes the PDT limitations, ensuring acute strong ROS killing properties and prolonged bacterial suppression for persistent gram-positive infections.

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